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TRANSLATIONAL AND CLINICAL RESEARCH |
in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells
a Department of Clinical and Experimental Medicine, Section of Haematology, University of Verona, Verona;
b Excellence Center of the University of Florence, DENOthe, Florence, Italy
Key Words. Mesenchymal stem cells • Immune suppression • Indoleamine 2,3-dioxygenase
Correspondence: Sergio Romagnani, M.D., Department of Internal Medicine, University of Florence, Viale Morgagni, 85, Firenze 50134, Italy. Telephone: 39-055-413663; Fax: 39-055-4271500; e-mail: s.romagnani{at}dmi.unifi.it
Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-
produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-. The suppressive effect of IFN- was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell– derived IFN-.
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